DPT - Biochemistry & Genetics - II (Metabolism of Carbohydrates) Glycolysis & its Regulation

DPT - Biochemistry & Genetics - II (4th Semester)

1. METABOLISM OF CARBOHYDRATES Glycolysis & its Regulation by , Miss Areesha Ahmad Lecturer

2. CONTENTS Harper's Biochemistry, 28th Ed. 2 Glycolysis Significance of Glycolysis Phases of Glycolysis Steps of Glycolysis Reaction of Glycolysis Reduction of Pyruvate to Lactate Regulations of Glycolysis References

3. GLYCOLYSIS Harper's Biochemistry, 28th Ed. 3 Glycolysis ( Glykys = sweet, lysis = splitting ) is main metabolic pathway for glucose, fructose, galactose and other carbohydrates derived from the diet. This was described by Embden, Meyerhof and Parnas , called as EMP pathway . Breakdown of 1mol of glucose ( 6C) to pyruvate ( 3C) and lactate in order to produce energy in the form of ATP is called glycolysis .

4. GLYCOLYSIS Harper's Biochemistry, 28th Ed. 4 It is the first step in carbohydrate catabolism. It is essential for brain which is dependent in glucose for energy. Comprises of the sequence of ten, enzyme catalyzed reactions . Glycolysis occurs in the cytosol of all cells. It is unique in that it can function either aerobically or anaerobically.

5. GLYCOLYSIS Harper's Biochemistry, 28th Ed. 5

6. SIGNIFICANCE OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 6 Glycolysis occur in every single cell (yeast, bacteria , humans). It represent the important set of biochemical catabolic reactions in all living cells. It is essential for aerobic respiration, anaerobic respiration as well as number of fermentations such as alcoholic fermentation , lactic acid fermentation etc. Aerobic respiration: oxygen is used to make energy

7. SIGNIFICANCE OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 7 The pyruvic acid (3C) produced at the end off glycolysis is available in the cell for further respiratory breakdown or for use in various other metabolic processes . The various intermediates compound formed during glycolytic breakdown can be diverted for a variety of intracellular biochemical processes.

8. PHASES OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 8 Energy Investment Phase (Preparatory Stage) Energy Generation Phase (pay off phase)

9. Harper's Biochemistry, 28th Ed. 9

10. STEPS OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 10

11. STEPS OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 11

12. REACTIONS OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 13 The Breakdown of Glucose to 2 molecules of pyruvate is drought about by the sequence of 10 reactions which can be divided into: Energy Investment Phase Energy Generation Phase

13. Harper's Biochemistry, 28th Ed. 14 Kinases are enzymes that  transfer phosphate groups from high-energy molecules to specific substrates. This process, called phosphorylation, 

14. Harper's Biochemistry, 28th Ed. 15 Isomerases are enzymes that catalyze the conversion of a molecule from one isomer to another. Isomers are molecules with the same atomic composition but different arrangements of chemical groups. 

15. Harper's Biochemistry, 28th Ed. 16 Kinases are enzymes that  transfer phosphate groups from high-energy molecules to specific substrates. This process, called phosphorylation, 

16. Aldolase is  an enzyme that helps the body break down sugars to produce energy

17. Isomerases are  a class of enzymes that convert a molecule from one isomer to another . Isomerases facilitate intramolecular rearrangements in which bonds are broken and formed. 

18. Reduction :  gain of hydrogen Dehydrogenases are enzymes that  catalyze the oxidation of organic compounds by transferring hydrogen atoms to electron acceptors .

19. Kinases are enzymes that  transfer phosphate groups from high-energy molecules to specific substrates. This process, called phosphorylation. The conversion of both ADP to ATP and ATP to ADP is a type of phosphorylation.

20. Mutase is an enzyme that  catalyzes the rearrangement of chemical groups within a molecule, specifically by moving a functional group from one position to another within the same molecule

21. Enolase , also known as phosphopyruvate hydratase , converts 2-phosphoglycerate (2-PG) into phosphoenolpyruvate (PEP) and water in the second to last step of glycolysis

22. 2 3

23. REDUCTION OF PYRUVATE TO LACTATE Harper's Biochemistry, 28th Ed. 26 Lactate, formed by the action of lactate dehydrogenase, is the final product of glycolysis in eukaryotic cells. The formation of lactate is the major fate for pyruvate in: Lens and cornea of the eye Kidneys Testes Leukocytes Red blood cells

24. REDUCTION OF PYRUVATE TO LACTATE LACTATE FORMATION IN MUSCLES Harper's Biochemistry, 28th Ed. 27 Dehydrogenases are enzymes that  transfer hydrogen atoms from organic compounds to electron acceptors,

25. Role of NADH in glycolysis Nicotinamide adenine dinucleotide (NADH) is a vital cofactor in cellular respiration and plays a role in glycolysis by acting as an electron carrier .  During glycolysis, NADH accepts electrons from glucose molecules and then transfers them to other molecules in the citric acid cycle.

26. REGULATION OF GLYCOLYSIS Harper's Biochemistry, 28th Ed. 29 Glycolysis is regulated by activating or inhibiting following key Glycolytic Enzymes Glucokinase & Hexokinase Phosphofructokinase Pyruvate Kinase Insulin favors glycolysis by activating these enzymes Insulin is a hormone our body makes to keep our blood glucose levels within the normal range. It is made by cells in the pancreas. Insulin's main job is to  move glucose from our bloodstream into the body's cells to make energy .

27. HEXOKINASE & GLUCOKINASE Harper's Biochemistry, 28th Ed. 30 Hexokinase is inhibited by Glucose 6 - Phosphate Glucokinase in the liver is not inhibited by G6P Hence , It can act only when there is plenty of Glucose

28. PHOSPHOFRUCTOKINASE (PFK) Harper's Biochemistry, 28th Ed. 31 It is the most rate- limiting enzymes. PFK is allosterically regulated enzyme ATP, Citrate are allosteric inhibitors Low pH has inhibitory effect on PFK AMP, ADP, F 6- P increase the activity of PFK Fructose 2,6- Biphosphate (F2, 6BP) is increase the activity of PFK. F2,6BP is formed from F6P by enzyme PFK- 2 Allosteric enzymes are enzymes that have an additional binding site for effector molecules, other than their active site. 

29. PYRUVATE KINASE It is most important regulatory enzyme of Glycolysis The Enzyme are inhibited by ATP. So, when ever energy is plenty in the cell, Glycolysis is inhibited F1,6- BP activate pyruvate kinase Insulin increase its activity where as Glucagon inhibits Harper's Biochemistry, 28th Ed. 32

30. METABOLIC FATE OF PYRUVATE Harper's Biochemistry, 28th Ed. 33

31. REFERENCES Textbook of Biochemistry, Sattaya Narayan, 5 th Edition . Harper's Biochemistry, 28th Ed. 34 Lippincott’s Illustrated Reviews : Biochemistry Fifth Edition Textbook of Medical Biochemistry, MN Chatterjea, 8 th Edition.

32. Harper's Biochemistry, 28th Ed. 35